General clinical information
A total number of 410 samples of pregnant women was recruited in this study, including 3 villus (0.73%, 3/410), 296 amniotic fluid (72.20%, 296/410), and 111 umbilical cord blood (27.07%, 111/410). The age of pregnant women varied from 19 to 42 years (mean at 24.33 ± 2.74 years), and gestational ages from 11 to 31 weeks (mean at 17.54 ± 3.17 weeks). The gestational ages in villus, amniotic fluid, and umbilical cord blood groups were 11+-13+, 18+-24+, and 24+-31+ weeks, respectively. As shown in Table 1, the prenatal samples are classified into ten subgroups according to clinical indications, including high age group (16.83%, 69/410), abnormal ultrasound group (44.39%, 182/410), high risk of serological screening in early or middle pregnancy group (6.10%, 25/410), fetuses with abnormal karyotypes group (3.17%, 13/410), patients with abnormal karyotypes group (2.93%, 12/410), adverse pregnancy history group (5.61%, 23/410), high risk of non-invasive prenatal testing (NIPT) group (1.22%, 5/410), two kinds of abnormal indications group (17.07%, 70/410), three kinds of abnormal indications group (0.73%, 3/410), and others group (1.95%, 8/410).
Diagnostic Efficacy Of Karyotyping For Chromosomal Abnormalities
In the 410 samples, the success rate of karyotyping was 99.27% (407/410). Only 3 cases of samples were not successful detected with karyotyping, including one villus, one amniotic fluid, and one umbilical cord blood. 47 samples (11.46%, 47/410) were shown with chromosomal abnormalities, including 13 cases of chromosomal numerical abnormalities (27.66%, 13/47), 26 cases of chromosomal structural abnormalities (55.32%, 26/47), and 8 cases of chimeras (17.02%, 8/47). The representative karyotyping of chromosomal numerical abnormality, structural abnormality and chimera were presented in Fig. 1–3, respectively. Among the 13 cases of chromosomal numerical abnormalities, including 5 cases of trisomy 21 (38.46%, 5/13), 2 cases of trisomy 18 (15.38%, 2/13), one case of 47, XYY (7.69%, 1/13), 4 cases of extra small marker chromosome (30.77%, 4/13), and one case of triploid (7.69%, 1/13).
Diagnostic Efficacy Of Cma For Chromosomal Abnormalities
In the 410 samples, the success rate of CMA was 100% (407/410). 61 (14.88%, 61/410) samples were found to have chromosomal abnormalities, including 10 cases of copy number variations (CNVs) (16.39%, 10/61), 9 cases of large fragment abnormality (≥ 10 Mb) (14.75%, 9/61), 38 cases of small fragment abnormality (< 10 Mb) (62.30%, 38/61) and 4 cases of heterozygous abnormality (6.56%, 4/61). Among the 9 cases of large fragment abnormality, including 4 cases of deletion (44.44%, 4/9), 3 cases of duplication (33.33%, 3/9), and 2 cases of deletion and duplication (22.22%, 2/9). Among the 38 cases of small fragment abnormality, including 14 cases of microdeletion (36.84%, 14/38) and 24 cases of microduplication (63.16%, 24/38). In addition, 31 (31/410, 7.56%) samples with normal karyotypes were found to have chromosomal abnormalities by CMA.
Diagnostic Values Of CMA And Karyotyping For Chromosomal Abnormalities
To investigate the potential diagnostic value of CMA and karyotyping for chromosomal abnormalities in PND, ROC curves were plotted on data from 410 samples. As presented in Fig. 4, representation of the data revealed the AUC of CMA was 0.93 (95% CI: 0.90 to 0.95), the sensitivity and specificity was 90.68% and 94.40%, respectively. The AUC of karyotyping was 0.90 (95% CI: 0.87 to 0.93) with 87.56% sensitivity and 91.22% specificity. Compared with karyotyping, the diagnostic value of CMA was remarkable for chromosomal abnormalities in PND.
Analysis of the relationships between the chromosomal abnormalities and clinical indications
As shown in Table 2, the rates of chromosomal abnormalities by karyotyping in high age group was 5.8%, in abnormal ultrasound group was 8.24%, in fetuses with abnormal karyotypes group was 76.92%, in patients with abnormal karyotypes group was 41.67%, in adverse pregnancy history group was 8.70%, in high risk of NIPT group was 20%, in two kinds of abnormal indications group was 11.43%, and in three kinds of abnormal indications group was 66.67%. The rates of chromosomal abnormalities by CMA in high age group was 1.45%, in abnormal ultrasound group was 14.84%, in high risk of serological screening in early or middle pregnancy group was 8.00%, in fetuses with abnormal karyotypes group was 61.54%, in patients with abnormal karyotypes group was 16.67%, in adverse pregnancy history group was 17.39%, in high risk of NIPT group was 20%, and in two kinds of abnormal indications group was 14.29%, in three kinds of abnormal indications group was 66.67%, and in others groups was 50.00%. There were no significant differences in chromosomal abnormalities of clinical indication groups by CMA and karyotyping.
Table 2
Analysis of the relationships between chromosomal abnormalities and clinical indications
Variables | Karyotyping (/n, %) | CMA (/n, %) | P |
High age | 4 (4/69, 5.80%) | 1 (1/69, 1.45%) | 0.37 |
Abnormal ultrasound | 15 (15/182, 8.24%) | 27 (27/182, 14.84%) | 0.07 |
High risk of serological screening in early or middle pregnancy | 0 (0/25, 0.00%) | 2 (2/25, 8.00%) | 0.49 |
Fetuses with abnormal karyotypes | 10 (10/13, 76.92%) | 8 (8/13, 61.54%) | 0.67 |
Patients with abnormal karyotypes | 5 (5/12, 41.67%) | 2 (2/12, 16.67%) | 0.37 |
Adverse pregnancy history | 2 (2/23, 8.70%) | 4 (4/23, 17.39%) | 0.67 |
High risk of NIPT | 1 (1/5, 20.00%) | 1 (1/5, 20.00%) | 1.00 |
Two kinds of abnormal indications | 8 (8/70, 11.43%) | 10 (10/70, 14.29%) | 0.80 |
Three kinds of abnormal indications | 2 (2/3, 66.67%) | 2 (2/3, 66.67%) | 1.00 |
Others | 0 (0/8, 0.00%) | 4 (4/8, 50.00%) | 0.08 |
CMA: chromosomal microarray analysis. |